Epoxidation and Metathesis of Limonene and Cannabidiol: New Compounds with Potential Biological Activity

• Grant number: 23/09638-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2029
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Dalmo Mandelli
• Grantee: Breno de Souza Bernardes
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 18/01258-5 - Novel chemical catalytic and photocatalytic processes for the direct conversion of methane and CO2 to products, AP.TEM

Abstract

This project proposes the use of natural products aiming to obtain functionalized molecules with higher added value through two central chemical transformations, epoxidation with H2O2 or O2 and cross-metathesis with reduced chain alkenes. Such transformations will be based on two starting materials of great relevance: limonene and cannabidiol. Limonene, the main component of orange peel oil (Brazil accounts for about 1/3 of the world's production of this fruit) has been tested, along with other terpenes, by the Research Group on Bio-Organic Chemistry and Bioactive Natural Products of the UFABC, in partnership with the Adolfo Lutz Institute, against Chagas disease and Leishmaniasis, as well as for cytotoxicity in human tumor cell lines. Cannabidiol is a terpenoid that has a reactive center for epoxidation and metathesis like that of limonene. Cannabidiol has been extensively studied in the treatment of neurological disorders among others. In the first step of the project, the epoxidation of limonene with H2O2 using MOFs (Metal-Organic Frameworks) based on different metals. The idea is to apply these materials already synthesized in our group, via the FAPESP thematic project in progress and which is being associated with this request. Then, the best catalysts will be applied in the epoxidation of cannabidiol. The results will be compared with those obtained with the classic green system based on Al2O3 and Ga2O3, developed by our group in the early 2000s in partnership with Netherlands and Belgium. In the second step, our experience gained from the 10-year partnership with the metathesis group at the University of Rennes 1 (France) will be applied in the metathesis of limonene and cannabidiol (as well as their epoxides) in the presence of functionalized reduced chain alkenes. The chemical transformations will initially be carried out in the presence of homogeneous Ru-based catalysts (Hoveyda-Grubbs, Zhan-1-B etc.) under mild conditions and with ecologically correct solvents (e.g., dimethylcarbonate). Then, a study of the heterogenization of Ru complexes (Hoveyda-Grubbs, Zhan-1-B, FixCatTM) will be carried out using MOFs as support, seeking to minimize Ru contamination in the products obtained. In a last step, the limonene derivatives will be evaluated for biological activity against Chagas disease, Leishmaniasis and melanoma. The unpublished derivatives of cannabidiol will be evaluated in the treatment of neurological disorders, in partnership with research groups from UFABC and UNIFESP. Part of the metathesis reactions will be carried out at Université de Rennes 1, through the BEPE project that is being detailed and attached to this FAPESP proposal.